Upstairs/downstairs: BHV-1, BRSV and where they attack

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All bovine respiratory disease is not the same. Some infections can be caused by a single pathogen, others need a combined effort to really bring an animal down. Where they attack the respiratory system is not always the same, either.

The upper respiratory tract is the first line of defense for the respiratory system, and one of the pathogens that targets it is bovine herpes-virus 1, or BHV-1, that causes infectious bovine rhinotracheitis (IBR).

John Ellis, DVM, PhD, Dipl. ACVP, Dipl. ACVM, Western College of Veterinary Medicine, Saskatoon, Saskatchewan, says the upper respiratory tract comprises the nasal cavity, sinuses, oropharynx, including the tonsils, and the trachea.

BHV-1 is not alone as far as targeting the upper airway. Ellis says bovine coronaviruses and reoviruses are known viral pathogens, and there are probably others. “Although Mannheimia hemolytica and Mycoplasma spp are generally associated with pneumonia, they are ‘commensal’ in the oropharynx and tonsils where they are generally kept in check in healthy immunocompetent, non-stressed cattle,” Ellis says.

Opening the door to pathogens

All of these pathogens have envelops or capsules that make them susceptible to dessication and UV light, but they are likely to survive for undetermined periods in moist conditions with favorable temperatures and out of sunlight, but Ellis notes that the limits of those conditions have not really been formally examined.

“I think that it is kind of interesting that in this era of hyperfocused molecular research, we still don’t know a lot about the basic biology of these pathogens in the environment; its just not likely to get funded,” he explains. Although transmission of these agents is generally associated with direct nose-to-nose contact or short-distance aerosol resulting from sneezing and coughing, undoubtedly, transmission on fomites or on the hands and instruments of veterinarians or cowboys occurs, it is just poorly documented.”

Inhalation would probably be thought to be the most common means of transmission, but certainly these pathogens can and do enter “orally” i.e. can be introduced to the oropharynx either through the mouth or by swallowing excess material that enters through the nose. “Certainly herpesviruses can cause ocular disease in a variety of species, including cattle and could be transported by the tear ducts from the eyes,” adds Ellis.

The respiratory system is designed to either block or push out pathogens and debris, but obviously the feedlot environment can overwhelm these defenses.

In the nose the turbulence and the convoluted structure of the nasal passages tends to trap particulate material including viruses and bacteria. Excess mucous with entrapped pathogens would enter the oropharynx and be swallowed. “In the trachea the so-called mucocilliary escalator traps particulates and moves the material toward the oropharynx where the excess mucous can again be swallowed or coughed out,” Ellis explains. “Mucous has some direct antimicrobial effects and would also contain variable amounts of type I (alpha) interferon and IgA which would have both non-specific and specific activity, respectively, against viruses and bacteria.”  

Environmental conditions such as cold, wind, dust and others can contribute to mechanical degradation of the upper airways, and pathogen load can also circumvent its immune defenses. “Environmental co-factors such as dry dusty conditions and high ammonia levels are intuitively recognized as factors that can compromise the non-specific micro-anatomical and physiological defense mechanisms in the respiratory tract,” Ellis says. “Perhaps less well appreciated and more subtle are nutritional factors such as micronutrients and dietary changes that can result in a relative acidosis or other physiological imbalances that can negatively impact on non-specific defenses.”

Clinical picture

BHV-1 enters epithelial cells (and eventually nerves) in the upper airways. Ellis says erosions and ulcers in the upper respiratory tract, notably the trachea, are the pathological hallmark of BHV-1 infections. These lesions occur from the lysis of infected cells which involves cell death by both necrosis and apoptosis, or programmed cell death. Widespread lysis of ciliated epithelium in the trachea disrupts the housekeeping functions of the mucociliary escalator, and results in a failure to clear bacteria from the upper airways, thereby resulting in deposition of bacteria in alveoli.

BHV-1 and recrudescence

“Stress” in the overall sense can lead to the recrudescence of latent herpesvirus infections. This has been classically and experimentally demonstrated by the administration of corticosteroids followed by the detection of BHV-1 in the upper respiratory tract of cattle. “Factors that can result in this physiological stress in the field are of course nebulous and would include such things as weaning, handling and transport of cattle, changes in environment and nutrition and infection,” Ellis says. “So, any animal is potentially a candidate to recrudesce  latent BHV-1.”

Ellis says this reactivation of latent virus is thought to be a critical event in the transmission of the virus and maintenance of it in cattle popula-tions. This phenomenon accounts for BHV-1 outbreaks in the absence of acute infection, i.e. In a “closed herd” or in a pen of feedlot cattle derived from the same ranch.

Experimentally peak shed of BHV-1 occurs about four days after infection, so this would be about the time when an individual animal would be most infectious. Shedding varies over a period of about 8 to 10 days after infection, and it can occur without many if any clinical signs.

 “Shedding is likely to vary with the particular isolate of BHV-1; some isolates probably replicate and shed at higher titers than others,” notes Ellis. “More efficient replication and resultant higher amounts of shed may be associated with increased virulence. Again, these basic questions about herpesvirus biology are poorly understood in cattle.”

Immunity to BHV-1

Immunity to BHV-1 is complex. Serum neutralizing (SN) antibody (IgG) is very important in protecting the calf from initial infection, however, BHV-1 can recrudesce in the presence of SN antibody, explains Jim Roth, DVM, PhD, Iowa State University. “Other components of the immune system are also important in protection from BHV-1 infection,” he says.

IgA in the nasal mucous can block BHV-1 from attaching to and infecting nasal epithelial cells. Memory T helper cells (CD4) will secrete interferon gamma when exposed to the virus, memory cytotoxic T cells (CD8) will kill BHV-1-infected cells before they can replicate the virus, and memory gamma delta T cells can help to control BHV-1 infection in the respiratory epithelium.

“We know that all of these types of memory T cells are induced after recovery from infection and after vaccination when modified-live vaccines are given to calves that lack maternal antibody,” Roth says. “The presence of maternal antibody seems to block MLV vaccines from inducing antibody and memory T cell responses. It is important to get a dose of vaccine into calves after the maternal antibody from colostrum is gone in order to get them protected against BHV-1.”

IBR treatment

There are specific anti-herpesviral drugs that are used clinically in other species, but these are not practical or economically feasible for use in cattle. Ellis adds that other than supportive care/good husbandry, there are really no practical specific treatments for BHV-1 in cattle. “Although BHV-1 has immunosuppressive capabilities, immunocompetent, non-stressed cattle infected with BHV-1, and for that matter other species infected with cognate alpha herpesviruses, will generally mount an efficient immune response and clear the infection without complications,” he says. “Of course, in the field many cattle that contact BHV-1 are stressed in a variety of ways and develop secondary bacterial infections subsequent to infection, and the immunosuppressive features of BHV-1 undoubtedly play a role in this common outcome.”

Herpesvirus infections can and often do “come back,” although often in a milder clinical form. At least two factors contribute to this phenomenon. If latency results from the primary infection, clinical “re-infection” or recrudescence can occur. It is not clear what the duration of clinical immunity to BHV-1 really is. “Certainly an animal that recovers from a primary herpesviral infection would usually have long-lived memory B and T cells, but these memory responses probably don’t prevent re-infection and a variable degree of clinical consequences in many animals.”

BHV-1 and calves

Depending on the immune status of the cow,  BHV-1-specific colostral antibodies can have significant disease-sparing effects in young calves. It has been shown that this effect can be enhanced by timely vaccination of cows. Colostrum also has numerous antimicrobial peptides and other factors that may affect some antiviral activities, although this has not been examined.

It is very unlikely that calves with BHV-1 infection acquired in utero would be born alive, given the multiorgan damage that BHV-1 causes in fetuses. It is theoretically possible for calves to acquire BHV-1 infections during the birth process if the cow has an active vaginal/vulval infection. “That occurs in humans with active HSV-1 infections and has been associated with fatal encephalitis in the newborn,” Ellis adds.

As with older cattle, young calves with poor or waning passive immunity can contract clinical BHV-1 infection in a variety of ways including nose-to-nose contact, short distance aerosols and on fomites. Ellis says, “Given that leukocytes can be infected actively and latently with BHV-1, it is also possible for calves to acquire BHV-1 infections by nursing, especially if the cow has low or no antibodies to BHV-1, but again, this is poorly documented.”

As in other respiratory diseases in cattle, it is always best to precondition calves; wean in a timely and as stress-free as possible manner, and vaccinate a couple of weeks later when the calves have adapted to life without mom. Ellis says whatever the timing of vaccination of calves, whether it be at pre-weaning or at weaning/branding, successful priming of the immune system is probably inversely related to the concentration of  BHV-1 maternal antibodies, so it is difficult to make overly general recommendations.

“Generally, if calves have good passive transfer, first vaccination at weaning/branding or about 3–4 months of age is probably the best and most practical protocol from the standpoint of the potential to successfully ‘immunize’ while avoiding the window of opportunity for infection of a highly susceptible, naïve calf. Vaccination on arrival at a feedlot is probably the worst ‘plan’, but it continues to be the industry standard, largely because it is convenient, and there is often no incentive for the cow-calf producer to vaccinate calves before sale.” Ellis notes that recent evidence has shown no benefit to giving a second vaccination for BHV-1 after the first vaccination in
the feedlot, although this remains controversial. 


How widespread is BHV-1?

BHV-1 infections are mostly thought of as a problem in feedlot cattle, which is true to a certain extent. This is probably largely due to the management of these cattle, which enhances spread of the virus among large, high-density populations of stressed, often naïve cattle, in other words a “perfect storm” for an epidemic.

“However, it is important to remember that BHV-1 has been found to be endemic in virtually all cattle populations that have been examined, except in some countries in Europe where it has been more or less eradicated,” explains John Ellis, DVM, PhD, Dipl. ACVP, Dipl. ACVM. “The reason why BHV-1 is not more of a problem in most dairy operations is probably because of routine vaccination and awareness of the importance of immunity to BHV-1 during heifer development.”



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